The long-range goal of the proposed work is to characterize the structure and chemistry of the system in the brain that underlies the maintenance of homeostasis. For this, we have utilized modern neuroanatomical techniques to clarify the organization of neural circuits in the rodent hypothalamus that express hypophysial neuropeptides, and to examine the regulation of neuropeptide gene expression by hormonal and neural inputs. Because this circuitry contains separate through interrelated components that mediate endocrine, autonomic, and behavioral responses, knowledge of its functional organization will almost certainly lead to important new insights into mechanisms underlying at least some forms of eating disorders, cardiovascular abnormalities, and psychiatric problems, including anxiety and depression. The proposed experiments are a direct extension of our previous work, and are designed to clarify the cellular distribution and developmental expression of recently cloned transcription factors in the hypothalamus, a well as to characterize the organization of a newly identified hypothalamic peptide, melanin-concentrating hormone (MCH). In one series of experiments, a newly developed combined retrograde transport/immunohistochemical/in situ hybridization method will be used to determine the cell type-specific expression of gonadal and thyroid hormone receptor, and retinoic acid receptor, in the paraventricular (PVH) and supraoptic (SO) nuclei of the hypothalamus, which contains separate groups of cells that project to the posterior pituitary, median eminence, and brainstem and spinal cord. The second series of experiments will use the same method to characterize the distribution of putative POU-domain transcription factors in the PVH/SO, and the third will utilize in situ hybridization to determine the developmental pattern of expression of this new class of homeodomain proteins. A final set of studies will employ combinations of immunohistochemical, hybridization histochemical and axonal transport methods at the light and ultrastructural levels to characterize the organization of the MCH (a posited corticotropin-inhibiting factor) and CRH-BP systems, with an emphasis on delineating their functional associations with stress-related neuroendocrine mechanisms that reside in the PVH and SO.